In situ forming polymer foams, such as the Arsenal Foam Technology commercialized by Arsenal Medical (Watertown, Mass.), have a number of important biomedical applications, including the prevention or treatment of hemorrhage, particularly from non-compressible or difficult-to-visualize wounds, vascular embolization, arteriovenous malformation, AV fistulas, space filling and bulking (e.g. following surgical resection, or for cosmetic purposes), prevention of tissue adhesion, hernia repair, prevention or treatment of reflux, and temporary or permanent occlusion of body lumens for a variety of applications including sterilization, prevention of calculus migration during lithotripsy, and other applications. The diversity of applications for in situ forming foams reflects significant advantages possessed by such foams relative to existing technology, including, without limitation their incorporation of well characterized, biocompatible materials; the ability to deliver in situ forming foams to closed cavities, for example intravascularly; the ability to deliver in situ forming foams to difficult-to-access body sites; the ability of in situ forming foams to expand into empty space or into space filled with blood, and the ability of the foam to fill a body cavity.
In situ forming foams are typically generated by delivering and mixing multiple liquid-phase components (such as a polyol component and an isocyanate component, which form a polyurethane foam). Each such liquid-phase component may comprise multiple different materials or agents that determine the mechanical properties of the foam and/or the kinetics of foam formation. Pores within the foam may be formed by a blowing reaction and/or by the entrainment of gas before or during foam formation. While blowing agents are effective to drive the foaming and expansion of in-situ forming foams, blowing agents or their byproducts may be toxic, and entrained gas may be preferred for applications in which such toxicity is preferably avoided.
In situ forming foams are particularly well suited to treating injuries in challenging settings such as in remote settings, and on the battlefield. However, in spite of their advantages, in situ forming foams have not been widely used because of the technical challenges associated with developing suitable in-situ foaming formulations for different applications and delivering such formulations to specific anatomical sites. Additionally, to maximize their efficacy in challenging settings such as on the battlefield, delivery systems for in situ forming foams should preferably be easy to assemble, provide a safe way to access the target site in the body, have a minimal number of parts, and rapidly aerate, mix, and deliver volumes of approximately 80-200 mL of in situ foaming formulations to patients. While low-viscosity materials can be aerated by simple shaking, gas entrainment poses a significant challenge in higher viscosity formulations, which may be necessary to generate foams having desirable physical and therapeutic characteristics.
There is, accordingly, a need in the art for delivery systems for efficiently delivering viscous gas-entrained in situ forming foam formulations to sites of interest in patients' bodies in non-clinical settings such as on the battlefield.